Using electrical signals to train the heart's muscle cells

Columbia Engineering researchers have shown, for the first time, that electrical stimulation of human heart muscle cells (cardiomyocytes) engineered from human stem cells aids their development and function. The team used electrical signals, designed to mimic those in a developing heart, to regulate and synchronize the beating properties of nascent cardiomyocytes, the cells that support the beating function of the heart. The study, led by Gordana Vunjak-Novakovic, The Mikati Foundation Professor of Biomedical Engineering and a professor of medical sciences (in medicine), is published online January 19 in Nature Communications.

Cardiovascular disease is one of the major health problems around the world, especially because the heart cannot repair itself: if cardiomyocytes are lost to injury or disease, they have only a minimal ability to regenerate. Scientists have been trying to develop ways to regenerate hearts by using cardiomyocytes grown from the patient's cells taken from skin or blood.
To be successful, these cardiomyocytes need to respond to and integrate with the surrounding heart muscle. But, currently, the immaturity and resultant irregular beating of human cardiomyocytes derived from stem cells have limited their usefulness for regenerative medicine and biological research.

"We've made an exciting discovery," says Vunjak-Novakovic. "We applied electrical stimulation to mature these cells, regulate their contractile function, and improve their ability to connect with each other. In fact, we trained the cell to adopt the beating pattern of the heart, improved the organization of important cardiac proteins, and helped the cells to become more adult-like. This preconditioning is an important step to generating robust cells that are useful for a wide range of applications including the study of cardiomyocyte biology, drug testing, and stem cell therapy. And we think that our method could lead to the reduction of arrhythmia during cell-based heart regeneration."

Vunjak-Novakovic worked with George Eng and Benjamin Lee, both of whom recently received their PhD from the Department of Biomedical Engineering. They are also MD students and the study's co-leading authors. The team grew human stem cell-derived cardiomyocytes and engineered them into three-dimensional structures. They then exposed these structures to electrical signals that mimicked those in a healthy heart--over just one week. They showed that this electrical stimulation increased cardiomyocyte connectivity and the regularity of muscle contraction.

The researchers plan to conduct fundamental studies of how the immature heart develops its beating function, and to investigate whether the "conditioned" cardiomyocytes will have the ability to seamlessly integrate with the heart muscle and provide a synchronized beating function.

"The heart is an organ of amazing complexity with about 3 billion cells that beat synchronously in response to electrical signals," Vunjak-Novakovic observes. "Our ability to recapitulate biology using bioengineering tools continues to drive our work and to be a source of inspiration. We are frequently reminded that this may be the best time ever to pursue biomedical engineering research!"
Benjamin Lee adds, "As a student in both engineering and medicine, I am particularly interested in how electrically conditioned cardiomyocytes can be used in a clinical context."

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Materials provided by Columbia University School of Engineering and Applied Science. Note: Content may be edited for style and length.

First Battery-Free Cellphone

University of Washington researchers have invented a cellphone that requires no batteries -- a major leap forward in moving beyond chargers, cords and dying phones. Instead, the phone harvests the few microwatts of power it requires from either ambient radio signals or light.

The team also made Skype calls using its battery-free phone, demonstrating that the prototype made of commercial, off-the-shelf components can receive and transmit speech and communicate with a base station.

The new technology is detailed in a paper published July 1 in the Proceedings of the Association for Computing Machinery on Interactive, Mobile, Wearable and Ubiquitous Technologies.
"We've built what we believe is the first functioning cellphone that consumes almost zero power," said co-author Shyam Gollakota, an associate professor in the Paul G. Allen School of Computer Science & Engineering at the UW. "To achieve the really, really low power consumption that you need to run a phone by harvesting energy from the environment, we had to fundamentally rethink how these devices are designed."

The team of UW computer scientists and electrical engineers eliminated a power-hungry step in most modern cellular transmissions -- converting analog signals that convey sound into digital data that a phone can understand. This process consumes so much energy that it's been impossible to design a phone that can rely on ambient power sources.

Instead, the battery-free cellphone takes advantage of tiny vibrations in a phone's microphone or speaker that occur when a person is talking into a phone or listening to a call.
An antenna connected to those components converts that motion into changes in standard analog radio signal emitted by a cellular base station. This process essentially encodes speech patterns in reflected radio signals in a way that uses almost no power.

To transmit speech, the phone uses vibrations from the device's microphone to encode speech patterns in the reflected signals. To receive speech, it converts encoded radio signals into sound vibrations that that are picked up by the phone's speaker. In the prototype device, the user presses a button to switch between these two "transmitting" and "listening" modes.
Using off-the-shelf components on a printed circuit board, the team demonstrated that the prototype can perform basic phone functions -- transmitting speech and data and receiving user input via buttons. Using Skype, researchers were able to receive incoming calls, dial out and place callers on hold with the battery-free phone.

"The cellphone is the device we depend on most today. So if there were one device you'd want to be able to use without batteries, it is the cellphone," said faculty lead Joshua Smith, professor in both the Allen School and UW's Department of Electrical Engineering. "The proof of concept we've developed is exciting today, and we think it could impact everyday devices in the future."
The team designed a custom base station to transmit and receive the radio signals. But that technology conceivably could be integrated into standard cellular network infrastructure or Wi-Fi routers now commonly used to make calls.

"You could imagine in the future that all cell towers or Wi-Fi routers could come with our base station technology embedded in it," said co-author Vamsi Talla, a former UW electrical engineering doctoral student and Allen School research associate. "And if every house has a Wi-Fi router in it, you could get battery-free cellphone coverage everywhere."
The battery-free phone does still require a small amount of energy to perform some operations. The prototype has a power budget of 3.5 microwatts.

The UW researchers demonstrated how to harvest this small amount of energy from two different sources. The battery-free phone prototype can operate on power gathered from ambient radio signals transmitted by a base station up to 31 feet away.

Using power harvested from ambient light with a tiny solar cell -- roughly the size of a grain of rice -- the device was able to communicate with a base station that was 50 feet away.
Many other battery-free technologies that rely on ambient energy sources, such as temperature sensors or an accelerometer, conserve power with intermittent operations. They take a reading and then "sleep" for a minute or two while they harvest enough energy to perform the next task. By contrast, a phone call requires the device to operate continuously for as long as the conversation lasts.
"You can't say hello and wait for a minute for the phone to go to sleep and harvest enough power to keep transmitting," said co-author Bryce Kellogg, a UW electrical engineering doctoral student.

"That's been the biggest challenge -- the amount of power you can actually gather from ambient radio or light is on the order of 1 or 10 microwatts. So real-time phone operations have been really hard to achieve without developing an entirely new approach to transmitting and receiving speech."

Next, the research team plans to focus on improving the battery-free phone's operating range and encrypting conversations to make them secure. The team is also working to stream video over a battery-free cellphone and add a visual display feature to the phone using low-power E-ink screens.

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Materials provided by University of Washington. Note: Content may be edited for style and length.